Journal Article

Tethering guides fusion-competent trans-SNARE assembly

Song, Hongki, Wickner, William

2019

Overview

R-SNAREs (soluble N-ethylmaleimide–sensitive factor receptor), Q-SNAREs, and Sec1/Munc18 (SM)-family proteins are essential for membrane fusion in exocytic and endocytic trafficking. The yeast vacuolar tethering/SM complex HOPS (homotypic fusion and vacuole protein sorting) increases the fusion of membranes bearing R-SNARE to those with 3Q-SNAREs far more than it enhances their trans-SNARE pairings. We now report that the fusion of these proteoliposomes is also supported by GST-PX or GST-FYVE, recombinant dimeric proteins which tether by binding the phosphoinositides in both membranes. GST-PX is purely a tether, as it supports fusion without SNARE recognition. GST-PX tethering supports the assembly of new, active SNARE complexes rather than enhancing the function of the fusion-inactive SNARE complexes which had spontaneously formed in the absence of a tether. When SNAREs are more disassembled, as by Sec17, Sec18, and ATP (adenosine triphosphate), HOPS is required, and GST-PX does not suffice. We propose a working model where tethering orients SNARE domains for parallel, active assembly.

• Publisher: National Academy of Sciences
• Subject: Adenosine Triphosphatases - chemistry / Adenosine Triphosphatases - genetics / Adenosine triphosphate / Adenosine Triphosphate - chemistry / Assembly / ATP / Biochemistry / Biological Sciences / Dismantling / Domains / Endocytosis - genetics / Exocytosis - genetics / Fusion protein / Glutathione Peroxidase - chemistry / Glutathione Peroxidase - genetics / Membrane fusion / Membrane Fusion - genetics / Membrane Fusion Proteins - chemistry / Membrane Fusion Proteins - genetics / Membranes / N-Ethylmaleimide / Phosphatidylinositols - chemistry / Phosphatidylinositols - metabolism / Phosphoinositides / Protein Multimerization - genetics / Protein transport / Protein Transport - genetics / Proteins / R-SNARE Proteins - chemistry / R-SNARE Proteins - genetics / Recombinant Proteins - chemistry / Saccharomyces cerevisiae - genetics / Saccharomyces cerevisiae Proteins - chemistry / Saccharomyces cerevisiae Proteins - genetics / SNAP receptors / Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins - chemistry / Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins - genetics / Tethering / Vacuoles - chemistry / Vacuoles - genetics / Vesicular Transport Proteins - chemistry / Vesicular Transport Proteins - genetics / Yeast